This application is related to the following the commonly assigned co-pending patent applications entitled, “MICROFLUIDIC VALVE”, Attorney Docket No.: 84569675, which is filed contemporaneously herewith and is incorporated herein by reference.
Microfluidics relates to the behavior, precise control and manipulation of fluids that are geometrically constrained to a small, typically sub-millimeter, scale. Numerous applications employ passive fluid control techniques such as capillary forces. In some applications, external actuation techniques are employed for a directed transport of fluid. For example, in some situations, rotary drives may be implemented to apply centrifugal forces.
Active microfluidics refers to a defined manipulation of the working fluid by active (micro) components such as micropumps or microvalves. Micropumps supply fluids in a continuous or intermittent manner for application such as for dosing of medicine. Microvalves determine the flow direction and/or the mode of movement of pumped liquids. In some examples, processes which are executed in a lab are miniaturized on a single chip in order to enhance efficiency and mobility as well as reducing sample and reagent volumes.
A lab-on-a-chip (LOC) is a device that integrates one or several laboratory functions on a single microelectronic/microfluidic chip that occupies millimeters to a few square centimeters to achieve automation and high-throughput screening. LOCs deal with the handling of small fluid volumes down to less than several picoliters (pL). Lab-on-a-chip devices are a subset of Micro-electro-mechanical systems (MEMS) devices and often referred to as “Micro Total Analysis Systems” (μTAS) as well.
This disclosure relates to a microfluidic valve network, which may be referred to as a microfluidic network. In some examples, the microfluidic network includes a first microfluidic valve that is connected between a first fluid reservoir and a fluid channel. A fluid-air interface is formed at an end of the first microfluidic valve and the fluid channel. A first meniscus of fluid from the first reservoir is formed at the fluid-air interface of the first microfluidic valve. A fluid agitator is positioned in the first microfluidic valve and is in contact with the fluid from the first reservoir. The fluid agitator is actuated by an electrical signal. The fluid agitator may be, for example, an electromechanical device (e.g., a piezoelectric device) or an electrical device (e.g., a thermal ink jet (TIJ) resistor). Upon actuation, the fluid agitator may agitate (e.g., heat or vibrate) fluid in the valve causing the fluid to break the first meniscus, allowing fluid from the first fluid reservoir to flow into the fluid channel.
In some examples, the microfluidic network also includes a second microfluidic valve that is coupled to a second microfluidic reservoir and the fluid channel. A second meniscus of fluid is formed at the fluid-air interface of the second microfluidic valve. In at least one example, the second microfluidic valve includes a fluid agitator that may also be actuated by an electrical signal to agitate fluid in the second microfluidic valve, causing the fluid to break the second meniscus. This allows fluid to flow from the second reservoir into the fluid channel. In at least one other example, the second microfluidic valve omits the fluid agitator. In this example, the fluid flowing from the first reservoir and into the fluid channel flows into the second meniscus, thereby breaking the second meniscus and causing fluid to flow from the second reservoir into the fluid channel. In either example, fluid from the first reservoir and fluid from the second reservoir is mixed together in the fluid channel.
In some examples, the fluid channel coupled to the first and second microfluidic valves may include a vent to allow air to flow out of the fluid channel, thereby drawing fluid from the first and second reservoirs into the fluid channel. Moreover, a time of the mixing may be controlled by the electrical signal (or multiple electrical signals). Many different configurations are possible for the microfluidic network. For instance, more than two microfluidic valves and/or multiple fluid channels may be employed to precisely control a sequence of mixing actions to result in a fluid with a particular volume and/or composition.
At least one of the microfluidic valves 24 includes a fluid agitator 30, which may be implemented as an electrical device (e.g., a TIJ resistor) or as an electromechanical device (e.g., a piezoelectric device). Each fluid agitator 30 may be actuated by an electrical signal. In examples where there is more than one fluid agitator 30, each fluid agitator 30 may be actuated by the same or different electrical signals to transition the microfluidic network from the rest state to an active state. Upon actuation, each fluid agitator 30 heats or vibrates fluid in a corresponding microfluidic valve 24 to break the meniscus of the corresponding microfluidic valve 24 and allow fluid to flow from a corresponding reservoir 8 into the fluid channel 26. Thus, in the active state, fluid freely flows into the fluid channel 26.
In some examples, a given microfluidic valve 24 includes the fluid agitator 30 and another microfluidic valve 24 omits the fluid agitator 30. In this situation, upon actuation of the fluid agitator 30 of the given microfluidic valve 24, fluid flows from a given (corresponding) reservoir 8 into the fluid channel 26 and contacts and breaks the meniscus of fluid formed at the other microfluidic valve 24 and allows fluid to flow from another (corresponding) reservoir 8 into the fluid channel 26.
A controller 32 may be programmed to provide the electrical signal to each fluid agitator 30. In some examples, the controller 32 may be a microcontroller or a field programmable gate array (FPGA) with input/output (I/O) pins for providing the electrical signals to the fluid agitators 30. In other examples, the controller 32 may be, for example, a computing device (e.g., a desktop computer, a laptop computer or server). In some situations, the controller 32 may actuate a first set (e.g., one or more) of the fluid agitators 30 in a first time period and the controller 32 may actuate a second set (e.g., one or more) of the fluid agitators 30 in a second time period to allow a delay between release fluids in the reservoirs 28.
By employment of the microfluidic network 20, tight controls of a timing, volume and/or composition of a resultant fluid in the fluid channel 26 may be achieved. In some examples, flowing the fluids from the reservoirs 28 into the fluid channel 26 may initiate a chemical reaction. In other examples, the fluids flowing from the reservoirs 28 into the fluid channel 26 may be mixed together to achieve a specific dilution rate (composition) for the resulting fluid in the fluid channel 26.
The first reservoir 56 provides fluid to the first microfluidic valve 52. The first microfluidic valve 52 may include a capillary tube 61 (or other elongated structure) that allows the flow of the fluid from the first reservoir 56 to an air-fluid interface at an end 62 of the first microfluidic valve 52. A meniscus of fluid forms at the air-fluid interface at the end 62 of the first microfluidic valve 52 and Laplace pressure generated by the meniscus prevents fluid from flowing in the fluid channel 58.
A fluid agitator 64 may be positioned in the capillary tube 61. The fluid agitator 64 may be in physical contact with the fluid present in the capillary tube 61 of the first microfluidic valve 52. The fluid agitator 64 may be actuated by an electrical stimulus, such as an electrical signal provided from a controller (not shown).
In some examples, the fluid agitator 64 may be implemented as an electrical device, such as a TIJ resistor. In such a situation, upon actuation by the electrical signal, the fluid agitator 64 heats the fluid in the capillary tube 61, forming a vapor bubble. The resultant vapor bubble applies pressure on the meniscus formed that the end 62 of the first microfluidic valve 52 and (upon sufficient pressure being built), breaks the meniscus, thereby allowing fluid to flow from the first reservoir 56 into the fluid channel 58 to transition the first microfluidic valve from a closed state to an open state.
More particularly, in examples where the fluid agitator 64 heats the fluid, the fluid agitator 64 may vaporize a (relatively small) portion of fluid in the capillary tube 61 in a timeframe of about one microsecond. The increased pressure of the vapor (“a drive bubble”) breaks the meniscus formed at the end 62 of the first microfluidic valve 52. In this manner, the mechanism for breaking the meniscus is similar to droplet ejection in an inkjet printer.
In other examples, the fluid agitator 64 may be implemented as an electro-mechanical device, such as a piezoelectric device (e.g., a crystal oscillator). In such a situation, upon actuation by the electrical signal, the fluid agitator 64 vibrates (oscillates) and applies pressure on the meniscus formed at the end 62 of the first microfluidic valve 52. Upon sufficient pressure being built by the vibration of the fluid agitator 64, the meniscus breaks, thereby allowing fluid to flow from the first reservoir 56 into the fluid channel 58.
The second reservoir 60 provides fluid to the second microfluidic valve 54. The second microfluidic valve 54 may include a capillary tube 65 (or other elongated structure) that allows the flow of the fluid from the second reservoir 60 to an air-fluid interface at an end 66 of the second microfluidic valve 54. A meniscus of fluid forms at the air-fluid interface at the end 66 of the second microfluidic valve 54 and Laplace pressure generated by the meniscus prevents fluid from flowing in the fluid channel 58.
Upon transitioning the first microfluidic valve 52 to the open state, fluid from the first reservoir 56 flows into the fluid channel 58. Upon contact of the fluid from the first microfluidic valve 52 with the meniscus at the end 66 of the second microfluidic valve 54, the meniscus breaks, thereby allowing fluid to flow from the second reservoir 60 into the fluid channel 58 to transition the second microfluidic valve 54 from a closed state to an open state.
As noted,
In some examples, the first microfluidic valve 52 and/or the second microfluidic valve 54 may be designed as (disposable) one-time-open valves. In other examples, the first microfluidic valve 52 and/or the second microfluidic valve 54 may be reused upon transitioning the microfluidic network 50 back to the rest state. To transition the microfluidic network 50 back to the rest state, fluid from the fluid channel 58, as well as fluid from the capillary tube 61 of the first microfluidic valve 52 and from the capillary tube 65 of the second microfluidic valve 54 may be extracted.
By employment of the microfluidic network 50, a composition, timing and/or volume of resulting fluid in the fluid channel 58 may be tightly controlled. For example, by controlling a volume of the fluid channel 58, the volume of the resultant fluid may be controlled. Additionally, in some examples, the fluids in first and second reservoirs 56 and 60 may be different fluids that (when combined) initiate a chemical reaction. In other examples, fluids in first and second reservoirs 56 and 60 may be fluids with a specific molar concentration that (when combined) mix together and result in a fluid with a particular molar concentration.
By employment of the microfluidic network 100, the volume, composition and timing of the fluid in the fluid channel 58 may be tightly controlled. In some examples, the fluid agitator 64 of the first microfluidic valve 52 may be actuated a predetermined amount of time before (or after) actuation of the fluid agitator 102 of the second microfluidic valve 54 to allow for specific amounts of the fluid from the first reservoir 56 and the second reservoir 60 to flow into the fluid channel 58. Such control of volumes allows for specific matching of ratios of reactants and reagents. Additionally, in situations where the fluid in the first and second reservoirs 60 are fluids with similar compositions but different molar concentrations, by controlling the timing of opening the first and second microfluidic valves 52 and 54, the resultant fluid in the fluid channel 58 may have a particular molar concentration.
Fluid flowing to an air-fluid interface at each of the N number of closed microfluidic valves 202 forms a meniscus to prevent (unwanted) fluid flow into the fluid channel 204. At least one of the N number of closed microfluidic valves 202 may include a fluid agitator (e.g., the fluid agitator 30 of
Breaking the meniscuses transitions the microfluidic network 200 from the rest state (illustrated in
The microfluidic network 200 illustrated in
Further still, in some examples, multiple closed microfluidic valves 202 may be opened (e.g., in response to an electrical signal to a fluid agitator) nearly simultaneously, which may be referred to as a “parallel valve opening”. For example, in the situation where there are four (4) closed microfluidic valves 202, a first and second microfluidic valve 202 may be opened nearly simultaneously (e.g., within about 100 milliseconds). In such a situation, the fluid channel 204 may be shaped to prevent breaking of the meniscus for the third and fourth microfluidic valves 202.
The microfluidic network 250 includes K number of fluid channels 252 that are interconnected with channel valves, where K is an integer greater than or equal to two. Each fluid channel 252 (or some subset thereof) may be a passive channel that allows fluids present to mix passively. Alternatively, each fluid channel 252 (or some subset thereof) may be an active channel that may include a wiggler mixer, an incubation chamber, a thermocycler or a combination thereof to accelerate a mixing rate. Each channel valve may be implemented in a manner similar to the first microfluidic valve 52 of
In the example illustrated in
In the state illustrated in
The microfluidic network 250 may be employed, for example, where a sequential combination of fluids is needed. For example, in situations where fluid controlled by the microfluidic valve 256 and 258 should be combined prior to combining the resulting mixture/compound with the fluid controlled by the closed microfluidic valve 262, the arrangement illustrated in
In
Inclusion of the buffer channel 304 prevents an unintended flowing of fluid, as described herein. For instance, as illustrated in
Additionally, sequentially and/or concurrently, the remaining J-1 closed microfluidic valves 302 (and microfluidic valves of corresponding buffer channels 304) may be opened (resulting in open microfluidic valves 310) to allow additional fluid to flow into the fluid channel 306, as illustrated in
The microfluidic network 300 may be employed, for example, where both sequential and parallel opening of the closed microfluidic valves 302 is needed. For example, in situations where complex DNA and/or medicine synthesis is being implemented, the tightly controlled order and volume of a mixing of fluids may be needed.
In operation, each of a plurality (or a single) of microfluidic valves may be opened to allow fluid to flow into one or more fluid channels of the microfluidic network module 352, in a manner described herein. Moreover, at a desired time, each of the channel valves 354 may be opened to allow fluid to flow between the microfluidic network module 352.
The microfluidic network 350 may be employed for example, where both sequential and parallel opening of the closed microfluidic valve 302 is needed. For example, in situations where complex DNA and/or medicine synthesis is being implemented, the tightly controlled order and volume of a mixing of fluids may be needed.
The microfluidic network 500 may further include a controller 516 that provides the first and the second electrical signal to the respective first fluid agitator 508 and the second fluid agitator 514. The fluid channel 506 may include a vent 518 that releases gas in the fluid channel to draw fluid from the first reservoir 504 and the second reservoir 512 into the fluid channel 506. Fluid from the first reservoir 504 and fluid from the second reservoir 512 mix in the fluid channel 506.
What have been described above are examples. It is, of course, not possible to describe every conceivable combination of structures, components, or methods, but one of ordinary skill in the art will recognize that many further combinations and permutations are possible. Accordingly, the invention is intended to embrace all such alterations, modifications, and variations that fall within the scope of this application, including the appended claims. Where the disclosure or claims recite “a,” “an,” “a first,” or “another” element, or the equivalent thereof, it should be interpreted to include one or more than one such element, neither requiring nor excluding two or more such elements. As used herein, the term “includes” means includes but not limited to, and the term “including” means including but not limited to. The term “based on” means based at least in part on.
Filing Document | Filing Date | Country | Kind |
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PCT/US2017/017983 | 2/15/2017 | WO | 00 |